We will conduct clinical trials with a large number of different Biologic Response Modifiers including combinations of agents and approaches. Given our expertise we believe that we are in a particularly good position to conduct Phase I trials of BRM's and have the broad and well established scientific base to appropriately generate and test scientific hypotheses and explore mechanisms of action of current biologic agents. We are in position to test the following: (1) approaches which utilize or modify immunologic mechanism: we have ongoing preclinical and clinical programs encompassing a range of agents and approaches including cytokines, (IL-2, IL-4, IL-7, IL-10 and IL-12), agents modifying the toxicity of cytokines (preclinical studies of NO synthase inhibitors such as amino guanidine, TNF inhibitors such as pentoxifylline), adoptive immunotherapies using antibodies (R24, Bec2) or cellular reagents (TIL, ANK), and cytokine gene therapies (IL-4); (2) approaches using naturally occurring or recombinantly produced regulatory molecules (ongoing clinical protocols of alpha interferon and transretinoic acid (TRA), preclinical studies of antisense molecules directed at fibroblast growth factor for the treatment of melanoma as well as monoclonal antibodies and related constructs (completed clinical trials of RF24 and proposed studies of the anti-idiotypic antibody, Bec-2), and (3) active clinical and preclinical programs in testing differentiation agents such as interferon, TRA and Suramin. (4) More approaches utilizing T-cell defined tumor epitopes in constructing tumor vaccine.